gms | German Medical Science

Ototoxicity is one of the typical side-effects of cisplatin. On the other side the chemotherapeutic carboplatin damages the inner ear structures very rarely. Previous pathophysiological examinations mainly refer to production of free radicals by cisplatin which cause oxidative cell injury. Additionally there is the possibility, that forming of Pt-DNA-adducts in the inner ear can be an additional cause of ototoxicity by blocking the transcription of DNA. Further examinations of this hyopthesis are presented by comparing the different forming of Pt-DNA-adducts in the inner ear induced by cisplatin or carboplatin respectively

Guinea pigs were injected intraperitoneally with a single dose of cisplatin or carboplatin respectively. After fixation of the cochlea the histologically slides were stained with DAPI and antibodies against Pt-DNA-adducts. 8, 24 and 48 hours after injection with cisplatin or carboplatin the staining of the stria vascularis as well as of the Reissner membrane were examined. Fluorescence of the adducts was normed onto the content of DNA of every nucleus and measured quantitatively.

After injection of cisplatin the Pt-DNA-adduct-concentration in the marginal cells of the stria vascularis was three times higher than in the basal and intermediate cells as well as in the cells of Reissner membrane. On the other side we do not see any significant increasing or differences in the measured cell populations after carboplatin exposition. Fluorescence signals of the outer hair cells also did not show a significant difference.

These comparing molecularbiological results support the above mentioned hypothesis that forming of Pt-DNA-adducts in the inner ear could be an additional cause of ototoxicity of cisplatin. The high accumulation of Pt-DNA-adducts in the marginal cells of the stria vascularis seems to play an important role in ototoxicity of cisplatin.

Supported by IFORES Essen, Germany